Abstract
BackgroundAccurate detection of characteristic proteins secreted by colon cancer tumor cells in biological fluids could serve as a biomarker for the disease. The aim of the present study was to identify and validate new serum biomarkers and demonstrate their potential usefulness for early diagnosis of colon cancer.MethodsThe study was organized in three sequential phases: 1) biomarker discovery, 2) technical and biological validation, and 3) proof of concept to test the potential clinical use of selected biomarkers. A prioritized subset of the differentially-expressed genes between tissue types (50 colon mucosa from cancer-free individuals and 100 normal-tumor pairs from colon cancer patients) was validated and further tested in a series of serum samples from 80 colon cancer cases, 23 patients with adenoma and 77 cancer-free controls.ResultsIn the discovery phase, 505 unique candidate biomarkers were identified, with highly significant results and high capacity to discriminate between the different tissue types. After a subsequent prioritization, all tested genes (N = 23) were successfully validated in tissue, and one of them, COL10A1, showed relevant differences in serum protein levels between controls, patients with adenoma (p = 0.0083) and colon cancer cases (p = 3.2e-6).ConclusionWe present a sequential process for the identification and further validation of biomarkers for early detection of colon cancer that identifies COL10A1 protein levels in serum as a potential diagnostic candidate to detect both adenoma lesions and tumor.ImpactThe use of a cheap serum test for colon cancer screening should improve its participation rates and contribute to decrease the burden of this disease.
Highlights
Colorectal cancer (CRC) is a leading cause of death worldwide, with over one million of new cases and half a million of deaths around the world every year [1]
Until further evidence is collected, current European guidelines accept the fecal occult blood test followed by confirmatory colonoscopy, which is therapeutic when resectable adenomas are identified [4]
The use of colonoscopy as a gold standard for CRC screening is controversial. It has reported higher sensitivity (97%) and specificity (98%) for early detection of CRC, but it has several pitfalls associated to it: increased economic cost; requirement of highly trained staff; uncomfortable bowel preparation; invasiveness; risk of morbidity and mortality attached to the procedure [7,8]
Summary
Colorectal cancer (CRC) is a leading cause of death worldwide, with over one million of new cases and half a million of deaths around the world every year [1]. Most population-based screening programs are using guaiac based fecal occult blood test, which biochemically detects small traces of blood derived from bleeding lesions in feces, or fecal immunological test, which is based on immunodetection of human hemoglobin in feces. These tests have a sensitivity of 80% for CRC and 28% for adenoma .1 cm, and specificities in the range of 91 to 94% [5]. The aim of the present study was to identify and validate new serum biomarkers and demonstrate their potential usefulness for early diagnosis of colon cancer
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